The mechanisms by which the complement system participates in the inflammatory response and the regulation of connective tissue metabolism continue to be examined. Several aspects of inflammation as well as resorption of bone are controlled by prostaglandins and current studies focus on the role of complement in the production of these mediators. In organ cultures of bone, complement activation initiated by antibodies reactive with cell surface antigens stimulates the synthesis of prostaglandins with resultant resorption of the bone. This effect is attributed to a macrophage-like cell present in the bone since prostaglandin production in cultures of peritoneal exudate macrophages is stimulated by antibody and rabbit complement. In the presence of the prostaglandin precursor, arachidonic acid, the synthesis of prostaglandins is markedly elevated, an effect which is inhibited by both steroid and non-steroid anti-inflammatory agents. Guinea pig and human sera are less effective complement sources. However, the stimulatory effects of complement from these species can be enhanced by The enzymatic removal of the sialic acd residues from the macrophage membrane, a process which favors activation of the alternative complement pathway.